The primary emphasis of the Superfund Hazardous Substances Basic Research Program, as described in the RFA, is the use of advanced basic research to improve the sensitivity and specificity of techniques for detecting adverse effects in humans or in ecological systems. Consistent with this emphasis, the theme for this project is sensitive toxic endpoints/sensitive populations for toxicity from chlorinated organic compounds. Chlorinated organic chemicals were selected as a subject of this theme in view of their importance as contaminants at Superfund and other hazardous waste sites, and because there is reason to suspect that adverse human and environmental impacts may be particularly a problem with low-level exposure to this class of contaminants. The program project consists of seven individual projects whose focus on improving sensitivity for detecting adverse effects of chlorinated compounds involves either: 1) study of mechanisms and dose-response relationships for health effects most likely to occur with environmentally-relevant exposures, viz. immune effects, reproductive/developmental effects, and cancer; 2) study of factors which lead to increased sensitivity (vulnerability) toxicity; 3) sensitive methods for detecting toxicity; or 4) sensitive methods for detecting/measuring contaminants in biological systems. The four individual projects are: Endocrine- Disrupting Effects of Chlorinated Hydrocarbons on Wildlife; Placental- Uterine Effects of Chlorinated Hydrocarbons; Dichloroacetate Kinetics, Metabolism and Human Toxicology; and Bioavailability of Superfund Chemicals. These projects will be supported by core facilities: Analytical Chemistry Core; Histology Core; Epidemiology/Biometrics Core; and Training and Outreach Core, as well as by administrative support made available by the program project. Three of the research projects are primarily or entirely biomedical in orientation, while one is primarily or entirely non-biomedical. Proposed research involves studies of toxicity in species ranging from fish and alligators to rats and mice to humans. These projects offer an integrated approach to advancing knowledge regarding the human and environmental impact of chlorinated organic contaminants.